Risk Stratification in NMIBC and Classification of Low-Grade, Intermediate-Risk Disease

A roundtable discussion, moderated by Christopher Wallis, MD, PhD, FRCSC, focused on patient selection and treatment considerations for non-muscle invasive bladder cancer, including recent data from SUO 2023. Dr. Wallis was joined by Sia Daneshmand, MD; Piyush Agarwal, MD; and Sima Porten, MD, MPH.

In the first segment of the roundtable series, the panel kicked off with conversations about risk stratification and classification of low-grade, intermediate-risk disease.

View the next segment on Current Evaluation and Treatment Pathways for Low-Grade, Intermediate-Risk NMIBC.

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Dr. Wallis: Hello, I’m Chris Wallace, a urologic oncologist at Mount Sinai Hospital and University Health Network in Toronto, Canada. Today, I’m joined by a distinguished panel to discuss recent advancements in non-muscle invasive bladder cancer. Let’s begin with introductions.

Dr. Daneshmand: Thank you. I’m Dr. Daneshmand, Director of Urologic Oncology at the University of Southern California in Los Angeles.

Dr. Agarwal: Hi, I’m Dr. Agarwal, Fellowship Director and Director of the Bladder Cancer Program at the University of Chicago.

Dr. Porten: Hello, I’m Dr. Porten, Fellowship Director and urologic oncologist at UCSF.

Dr. Wallis: Thank you all. Today, we’ll delve into the rapidly evolving field of non-muscle invasive bladder cancer, experiencing notable changes in recent years. To set the stage, could one of you provide an overview of the AUA/SUO risk stratification for non-muscle invasive bladder cancer? It’s crucial to recognize the diversity within this patient population.

Dr. Daneshmand: Certainly, I can cover the AUA guidelines. They categorize patients into low-, intermediate-, and high-risk groups. High-grade disease larger than 3 centimeters, including CIS, high-grade T1, falls into the high-risk category. Low-risk patients have low-grade TA tumors or small high-grade tumors, distinguishing them from the AUA and EAU guidelines. Intermediate-risk encompasses cases like high-grade TA tumors larger than 3 centimeters or recurrent low-grade tumors, necessitating a distinct approach due to a higher recurrence risk.

Dr. Agarwal: There are nuances in staging; for instance, a low-grade T1 may be considered intermediate-risk. Some debate exists about high-grade TA tumors less than 3 centimeters, with varying opinions on their categorization. Additionally, recent EAU guidelines highlight very high-risk patients over 70 with specific criteria such as variant histology and lymphovascular invasion.

Dr. Porten: As more data emerges, refinement of risk stratification tools will likely occur. The AUA guidelines also identify a very high-risk subgroup with stars, including variant histology and lymphovascular invasion, demanding careful consideration.

Dr. Wallis: Indeed, the landscape is dynamic. Moving forward, considering the heterogeneity within intermediate-risk patients, what features define a low-grade patient versus an intermediate-risk patient?

Dr. Agarwal: For intermediate-risk, multifocal tumors, tumors larger than 3 centimeters, and early recurrences within a year from a previous low-grade tumor elevate the risk level. Measurement of tumor size poses challenges, but the loop technique, using the scope width for estimation, is a practical approach. Size estimation becomes more complex for tumors with varying characteristics, and imaging studies can aid in certain cases.

Dr. Wallis: A pertinent question arises when discussing tumor size estimation during resection. Any thoughts on how to accurately measure tumors during the resection process?

Dr. Daneshmand: Measuring tumor size during resection is challenging, especially around the 3-centimeter cutoff for risk categorization. The loop technique, where the scope width determines size, is commonly used. However, accuracy diminishes with varying tumor characteristics. Imaging studies and post-resection assessment can provide additional insights. The challenge lies in distinguishing size accurately, especially for tumors with complex features.

Dr. Porten: Additionally, pathologists contribute to size estimation in the post-resection phase, providing a gross description and measuring the tumor in 3 sections. It’s an estimation that adds some subjectivity, but it aids in determining small, medium, or large tumors.

Dr. Wallis: With these risk groups serving as a guide, let’s delve into the goals of therapy. How do you view progression risks versus recurrence risks for these patients, and how does this influence our approach to therapy?

Dr. Porten: Both progression and recurrence risks are considerations in therapy planning. Preventing grade reclassification to high-grade disease in recurrent low-grade cases, affecting about 10-15% of patients, is crucial for patient health. Recurrences, while not immediately life-threatening, can significantly impact quality of life. A balanced approach aims to mitigate both progression and recurrence risks, ensuring patients lead fulfilling lives free of pain and side effects.

Dr. Agarwal: Conditional risk and progression studies indicate that the longer patients remain tumor-free, the lower the progression and recurrence rates. Recurrences within short intervals, typically every 3 months, pose higher risks. A 6-month interval reduces the recurrence rate to about 31%, with a 7% to 8% progression rate at 2 years. Frequent recurrences suggest a more aggressive phenotype, prompting consideration for treatment.

Dr. Wallis: The heterogeneity of non-muscle invasive bladder cancer poses a challenge. Any thoughts on how the varied tumor phenotypes impact our understanding of the disease and its management?

Dr. Agarwal: The heterogeneity within this tumor type complicates our approach. Differentiating between tumor subtypes, considering their unique characteristics, becomes crucial. For instance, tumors with frequent recurrences may exhibit a more aggressive phenotype, demanding tailored treatment strategies. The evolving understanding of these phenotypic variations is essential for optimizing patient outcomes.